PB2148: EFFICACY OF SMALL MOLECULE TARGET THERAPIES IN REFRACTORY OR RELAPSED DIFFUSE LARGE B-CELL LYMPHOMA AND MOLECULAR SUBTYPING: A MULTI-CENTER REAL-WORLD EVIDENCE
Authors: Y. Zhang, Y. Hou, X. Zhou, L. Sun, W. Wang, Y. Wo, Y. Sun, Q. Xu, P. Liu
Journal: HemaSphere (2022)

Background: Diffuse large B-cell lymphoma (DLBCL) shows remarkable molecular heterogeneity that can demonstrates different clinical outcomes. The two major cell-of-origin (COO) subtypes, germinal center B cell-like (GCB) and activated B cell-like (ABC) lymphomas, have been transcriptionally defined. Small molecule target therapies such as lenalidomide and Bruton’s tyrosine kinase (BTK) inhibitor have been widely used for refractory or relapsed DLBCL (R/R DLBCL) in the chemo-free manner or in combo therapy together with salvage chemotherapy. Aims: To reveal the efficacy and administration scenario of lenalidomide and BTK inhibitor in R/R DLBCL with molecular subtyping of COO. Methods: Real-world data of R/R DLBCL patients exposure to lenalidomide and BTK inhibitor in the chemo-free manner or in combo therapy together with salvage chemotherapy were extracted into the current study from the national medical center as well as regional medical centers. Archived tumor samples of included R/R DLBCL patients were submitted to COO subtyping with DLBCL-COO assay (Canhelp Genomics, Hangzhou, China). Results: Ninety-one patients were registered into current study, 43 (47.3%) of which received BTK inhibitors (ibrutinib, acalabrutinib, or zanubrutinib) and/or lenalidomide chemo-free therapies (chemo-free therapy) and 48 (52.7%) of which received BTK inhibitors (ibrutinib, acalabrutinib, or zanubrutinib) and/or lenalidomide combo therapy with cytotoxic regimen (combo therapy). The most common administrated cytotoxic regimen with BTK inhibitors and/or lenalidomide were: R2 (rituximab plus lenalidomide) in 11 patients, lenalidomide in 10 patients and R2-GEMOX in 9 patients. The median age was 64.5, male to female ratio was 1.08:1. The proportion of patients receiving second-line and further lines of therapy in “combo cohort” and “chemo-free cohort” were 82% and 18% vs. 62% and 38%, respectively. Less lines of prior systemic therapies was seen in “combo cohort”. Overall response rate was 48.4% with 19.8% complete remission rate. The median progression free survival was 4 months. 35.2% patients was GCB subtype and 41.8% patients was ABC subtype. There was no significant difference regarding ORR between GCB and ABC subtype in the whole population (43.8% vs. 60.5%, P=0.23). However, significantly higher ORR was identified in patients with ABC subtype receiving “combo therapy” (GCB: 26.7% vs. ABC: 65.2%, P=0.044), which was not observed in “chemo-free therapy” (GCB: 58.8% vs. ABC: 53.3%, P=1). Other clinical-pathologic parameters were not associated with ORR. Summary/Conclusion: Small molecule target therapies are more commonly administrated with cytotoxic regimen in the real world, and its efficacy is different from the one in the clinical trial. A considerable proportion GCB subtype R/R DLBCL received BTK inhibitor and/or lenalidomide. Molecular subtyping predicts the clinical benefit for patients with combo therapies, instead of the chemo-free therapies, in which heavier prior treatment may significantly impact the clinical outcome.